Cause Of Megaloblastic Anemia Research Articles

Retrospective evaluation of patients with vitamin B12 deficiency in the pediatrics outpatient clinic

Background/Aim: This study examines patients diagnosed with vitamin B12 deficiency in our department. Although rare, vitamin B12 deficiency is one of the causes of megaloblastic anemia, which can lead to negative outcomes in patients. We aim to promote earlier diagnosis to protect patients from these negative effects. Therefore, this study will contribute to raising awareness in the literature. Methods: Retrospectively, we included a total of 127 outpatient children, aged 0–18 years (0–215 months), who were diagnosed and treated for vitamin B12 deficiency at the Bagcilar Training and Research Hospital Child Health and Disease Clinic between October 2014 and February 2015. Results: Among the patients, 67 (53%) with vitamin B12 deficiency were female, while 60 (47%) were male, indicating a higher occurrence in girls. Vitamin B12 deficiency was most commonly observed in the age groups of 0-2 years and 12-17 years (adolescents). The mean vitamin B12 level was 168.1 (34.1) pg/mL, the mean hemoglobin level was 12 (1.9) g/dL, and the mean MCV (mean corpuscular volume) was 78.4 (8.1) fl. Anemia was observed in 38% of the patients, bicytopenia in 4%, neutropenia in 6%, thrombocytopenia in 9%, pancytopenia in 3%, and macrocytosis in 2%. Non-iron-deficient patients showed no difference in mean hemoglobin and RDW (red cell distribution width) when compared to iron-deficient patients. However, their B12 levels were lower. The prevalence of iron deficiency did not differ between girls and boys. Comparing patients with vitamin B12 levels lower than 150 pg/mL to those with higher levels, there were no significant differences in average Hb, MCV, and RDW. Conclusion: It should be noted that macrocytic anemia is not exclusive to vitamin B12 deficiency. Vitamin B12 deficiency can manifest as normocytic anemia and should not be overlooked in biochemical assessments. It is recommended to conduct nationwide and regional prevalence studies to evaluate vitamin B12 deficiency as a public health issue and to develop new solutions accordingly.

Knuckle hyperpigmentation in a young male: A clinical sign of B12 deficiency not to be missed.

Vitamin B12 and folate deficiency are reversible causes of megaloblastic anemia. Strict vegetarians are at risk of megaloblastic anemia due to low cobalamin in their diet. Knuckle hyperpigmentation in patients with megaloblastic anemia is due to excess melanin synthesis in skin. Here we present a case of a young vegetarian male with megaloblastic anemia with knuckle hyperpigmentation managed successfully with intravenous followed by oral vitamin b12 and folate supplementation.

Thiamine-Responsive Megaloblastic Anemia Syndrome Combined with Thalassemia Trait: A Rare Association

Abstract Introduction Thiamine-responsive megaloblastic anemia syndrome (TRMA, OMIM reference 249270), also known as Rogers' syndrome, is a rare type of anemia characterized by the triad megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus (DM). Disturbance of thiamine transport into cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case Report We report the case of an 8-year-old girl who presented at age 4 years with anemia. She had a combined hematological profile of microcytic and macrocytic anemia. The parents refused bone marrow aspiration and genetic diagnosis. Hemoglobin electrophoresis established the thalassemia trait. She was later confirmed to have sensorineural deafness and monogenic DM. A tentative TRMA diagnosis was based on megaloblastic anemia, sensorineural deafness, and monogenic DM triad. The patient was treated empirically with a daily dose of thiamine 200 mg; her hemoglobin level normalized, but the deafness and DM did not improve. Conclusion In routine practice, patients with TRMA must be evaluated thoroughly for other causes of megaloblastic anemia, including therapeutic thiamine trials in the presence of sensorineural deafness or DM. These patients should be followed throughout their life span both for DM and to control their response to thiamine therapy for megaloblastic anemia.

The Intake of Junk Food as an Etiological Factor of Megaloblastic Anemia in Patients visiting Mayo Hospital, Lahore

Objective: The study was performed to determine role of junk food intake in the development of megaloblastic anemia.
 Methodology: It was a clinical based cross-sectional study conducted at Mayo Hospital Lahore in collaboration with Pathology Department of King Edward Medical University from June 2017 to June 2021. All the patients of age 7 to 70 years including males and non-pregnant females attending the Out Patient Department or admitted in the hospital and having hemoglobin values<12 gm/l, MCV more than 95 fl and bone marrow examination suggestive of a megaloblastic change in the marrow (WHO criteria)were included in our study. The patients who had received blood transfusion or hematinic in less than 6 months before diagnosis and pregnant females were excluded from our study. A total 1333 patients were screened, out of which only 160 patients were diagnosed with megaloblastic anemia who had undergone bone marrow trephine biopsy. Their dietary history was taken in detail and history of depression was noted on validated questionnaires. The obtained data was analyzed on the basis of age groups (7-25 years, 26-50 years, 51-75 years) using SPSS descriptive analysis and results were formulated.
 Results: The study revealed that 160 (12%) of total 1333 patients were diagnosed with megaloblastic anemia on bone marrow trephine biopsy with male to female ratio of 1:1.28. Total 58 (36%) patients belonged to 1-25 years age group 68 (43%) patients to 26-50 years age group and 34 (21%) patients belonged to 51-75 years age group. Junk food consumption was seen (60.3%) in 7-25 years age group as a prevalent etiological factor.
 Conclusion: Junk food consumption is the major cause of megaloblastic anemia in young population and poor diet in middle age group, whereas comorbidities are the major etiological factor in older people.

Prevalence and clinic hematological profile of vitamin B12 deficiency associated megaloblastic anemia in children of Jammu region - A hospital based observational study

: Vitamin B12 deficiency (VBD) Megaloblastic Anemia (MA) is a relatively common disease encountered by pediatricians in Jammu region of north India, yet the data on prevalence of VBD in this age group remains scarce. Hence this study was conducted to study the prevalence and clinic hematological profile of VBD associated MA in children between 6 months to 18 years of age. To estimate the prevalence and clinico hematological profile of vitamin B12 deficiency associated MA in children between 6 months to 18 years, who were admitted in SMGS Hospital, Government Medical College Jammu. A Retrospective cross sectional study was conducted in children between 6 months to 18 years, who were admitted in SMGS Hospital, Government Medical College Jammu with diagnosis of Nutritional Anemia from April 2020 - March 2021.Case records of patients were reviewed for vitamin B12 deficiency as a cause of MA who were included in study. Vitamin B12 deficiency was diagnosed by measuring B12 levels in blood and by bone marrow examination if required. Clinic hematological profile of the participants was observed by reviewing their records for age, sex, socioeconomic status, food habits, presenting complaints, clinical signs and symptoms, peripheral smear findings and need for transfusion. All descriptive data collected was represented by tables and evaluated for statistical outcomes. The prevalence of vit. B12 deficiency associated MA in our study is 16.66 %. Among them 60% were females and 40% males. Age wise distribution was 6months -1 year 20 %, 1-5 years 22%, 6-10years 16% and 11-18 years was 42%. Vitamin B12 deficiency was more prevalent in lower socioeconomic group 80% and in those who were vegetarians 60%. Anorexia, generalised weakness, pallor was observed in 100% subjects. Neurologic involvement in the form of irritability, tremors was present in 30%. Icterus was seen in 10% while hepatomegaly and splenomegaly was present in 20 % and 22% respectively. Edema was seen in 2% of the subjects. Hyperpigmentation of knuckles was observed in 86% of the patients. Macrocytic anemia (MCV >100 ug/L) was observed in 100%. Bicytopenia was seen in 80% while Pancytopenia was present in 20%. Among 150 cases of Megaloblastic Anemia 80% of the patients were diagnosed by Vitamin B12 essay, 20% were diagnosed by Bone marrow examination. Blood transfusion secondary to severe anemia was required in about 10%. Vitamin B12 deficiency is not that uncommon in our population with prevalence of 16.66% in hospitalized children. However true prevalence can only be estimated by population based surveys in pediatric age group. The most common presenting complaint in Megaloblastic Anemia is anorexia, generalised weakness, irritability manifesting clinically as pallor, hyperpigmentation of knuckles and hematologically as macrocytic anemia with 80% bicytopenia and 20% pancytopenia. Thus vitamin B12 addition in anaemia control and prophylaxis programmes may be considered.

Prevalence of megaloblastic anaemia and its causative factors in a tertiary care centre at Western India

Background: Anaemia affected population includes male, females as well as children and is a common problem that has been seen in western India. Megaloblastic Anaemia is common in India but regarding its prevalence and causative factors data is insufficient. The most common cause of megaloblastic anaemia includes deficiency of folic acid and Vitamin B12. Due to vegetarian lifestyle of the people the deficiency of Vitamin B12 is more common rather than the other macronutrient. In today's time, only iron and folic acid is provided by Anaemia control or prophylaxis program. This issue needs focus and hence this study has been chosen.Objective: To focus on the incidences of Megaloblastic Anaemia in Western India and analyse the possible causative factors.Materials and Methods: Patients with a haemoglobin <10 g/dl and peripheral smear findings consistent with megaloblastic anaemia present in the hospital over a period of 2 months will be included in the study. Patient's diet, drug intake, present symptoms and other history will be taken into account. Recording of complete blood counts, peripheral film examination, reticulocyte count and cobalamin and folate assays will be done. Patients suffering from chronic disease like renal disease, cancer, tuberculosis, liver disease etc., Will be excluded from the study. All data will be collected and statistically evaluated.Results: In the current study, 500 patients who were admitted to the gynaecology, paediatric, and medical wards were all assessed. These patients were all eligible to participate. They were divided into three groups based on the mean corpuscular volume (MCV) value, serum assay, and peripheral smear results: Macrocytic, normocytic, and microcytic anaemia. A megaloblastic blood film or low serum indicators along with the normal MCV value were categorised as having macrocytic anaemia. A total of 100 patients had macrocytic anaemia identified. The distribution of sexes was: 70 (male), 30 (female). There were discovered to be 55% of patients with cobalamin deficit and 8% of patients with folate deficiency. Every patient were vegetarians, coming from a poor socioeconomic status.Conclusion: The diagnosis of Megaloblastic anaemia was done through complete blood counts, red cells and assays of two vitamins. Majority of patients having megaloblastic anaemia was due to deficiency of cobalamin. Poor diet in cobalamin or folate were the contributing factors in Megaloblastic anaemia. Prevention can be done through awareness camps and education programmes and also through proper diet. Vitamin B12 should be included in the diet of patients along with iron and folic acid.

The Screening and Treatment of Vitamin B12 Deficiency

Vitamin B12 deficiency is now more prevalent than ever. It is a common cause of megaloblastic anemia, neuropsychiatric disorders, and other clinical manifestations. Screening is required in patients with single or multiple risk factors. Measurement of serum methylmalonic acid can be used to confirm deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12. Oral administration of high-dose vitamin B12 as well as intramuscular administration are effective as corrective therapy. This review briefs about the pharmacokinetics and pharmacodynamics of Vitamin B12, risk factors associated with its deficiency, screening methods and treatment options.

Imerslund-Grasbeck syndrome- a rare cause of megaloblastic anemia in an infant with homozygous mutation in CUBN gene: a case report and review of the literature

Megaloblastic anaemia is one of the important causes of pancytopenia in children and nutritional deficiencies of vitamin B12 and folate are the most common causes comprising 95% of these cases. Defects in absorption, transport and metabolism of vitamin B12 are well described, however, are very rare. We report a rare case of Imersland Grasbeck syndrome, in an infant who presented with pancytopenia, with defective absorption of B12-intrinsic factor complex at the ileum and defective tubular reabsorption of proteins in renal tubule due to same protein defect caused by mutations in two genes – CUBN (cubilin) and AMN (amnionless).

Folate Deficiency in an Urban Safety Net Population

Introduction: Folate deficiency is a known cause of megaloblastic anemia. Serum folate level is therefore a common component of the workup for megaloblastic and other anemias. Following mandatory fortification of grain products with folic acid in the US in 1998, folate deficiency has become relatively rare in both the general population and in hospitalized patients. Some authors have suggested that serum folate levels should be tested rarely if at all in countries with mandatory folic acid fortification given low rates of deficiency, high cost per diagnosis of deficiency, and low rates of supplementation for those found to be deficient. However, given persistent racial, ethnic, and socioeconomic disparities in folate deficiency, these conclusions may not apply to all populations. In this study, we examine the rate at which serum folate testing detected folate deficiency in an urban safety net hospital and the characteristics of patients found to be folate deficient. Methods: All serum folate tests performed on inpatients and emergency department patients in 2018 at a large safety net hospital in Boston were reviewed. Serum folate levels under 4 ng/mL were considered deficient per WHO criteria. We reviewed the charts of all patients found to be folate deficient, collecting demographic data; data concerning social determinants of health; and clinical data such as hematologic lab data, stated reason for testing, and pertinent disease states such as malnutrition and substance use. We also noted whether the medical team acted upon the folate deficiency. Finally, we performed a cost analysis. Results: Out of 1368 patients whose serum folate was tested, 76 patients (5.5%) met criteria for folate deficiency. Of those patients, chart review found that hematologic abnormality was a documented cause of testing for 63%. Overall, 79% of folate deficient patients were anemic, but only 20% had a macrocytic anemia. 42% had a documented diagnosis of malnutrition. Common social determinants in patients found to be folate deficient include birth outside of the US (25%), homelessness (12%), and alcohol use disorder (29%). Of those found to be folate deficient, 93% were either started on folic acid supplementation or had already been prescribed supplementation prior to testing (5%). Given that our institution charges $71 per folate test, the expected charges per deficient test would total $1278. Discussion: While the decreased incidence of folate deficiency after fortification has led many to conclude that serum folate tests have limited utility, our data show that this conclusion may not apply to all populations. The 5.5% rate with which testing detects folate deficiency at our institution, with 46% of 2018 income from Medicaid, was markedly higher than the 0.4% rate reported in a similar study done at nearby hospital that derived 14% of 2018 income from Medicaid (Theisen-Toupal et al. J Hosp. Med. 2013). Comparisons to other studies are limited, as the cutoff for folate deficiency varies significantly between institutions. However, the markedly higher frequency with which folate deficiency was detected at our institution as compared to others suggests that folate testing may still have a role within safety net and many public hospital systems. In addition, serum folate testing may be more cost effective at such hospitals. At our hospital, the charge per deficient folate test was $1278, while previously published data from the nearby hospital described above showed a charge of over $35,000 per result under 4 ng/mL (Theisen-Toupal et al. J Hosp Med 2013). In addition, our results showed that deficient folate results usually prompted change in management. At our hospital, over 90% of folate deficient patients were prescribed a folic acid supplement at discharge, while prior studies reported rates of supplementation in the range of 0-65% (e.g. Ashraf et al. J Gen Intern Med 2008). This may reflect greater cognizance among our providers of nutritional deficiencies associated with social determinants of health common to our patient population. As our results indicated high rates of anemia, malnutrition, immigrant status, and substance use disorders among folate deficient patients, future research may include comparisons between patients found to have normal vs low folate levels. Identifying correlations between folate deficiency and other patient characteristics may help to target testing towards those most likely to benefit. Disclosures No relevant conflicts of interest to declare.

&lt;p&gt;Metformin Treatment: A Potential Cause of Megaloblastic Anemia in Patients with Type 2 Diabetes Mellitus&lt;/p&gt;

IntroductionVitamin B12 (cobalamin) deficiency is a frequent cause of megaloblastic anemia, manifested through various symptoms. Screening for this deficiency can be justified in case of patients with one or more risk factors present from the following: gastric resections, inflammatory bowel disease, use of metformin over a prolonged period of time, administration of proton pump inhibitors or H2 histamine receptor blockers for more than 12 months and in case of adults over 75 years of age. One method of determining vitamin B12 deficiency is measuring its serum levels, as well as performing measurements of serum levels of methylmalonic acid and homocysteine levels, which experience an increase in the early stages of vitamin B12 deficiency.Clinical CaseWe bring to your attention, the case of a 62 years old patient diagnosed with Type 2 Diabetes Mellitus in 2015 that presented in the emergency room in October 2019 with an altered general condition, nausea, vomiting, abdominal pain, palpitation, and dyspnea. Treatment with metformin was initiated from the diagnosis of Type 2 Diabetes Mellitus, four years before. Investigations established the diagnosis of megaloblastic anemia by vitamin B12 deficiency. The symptoms disappeared after the injection of vitamin B12.ConclusionPeriodical dosing of vitamin B12 should be performed in the case of patients with Type 2 Diabetes Mellitus treated with metformin, especially if they associate anemia and/or peripheral diabetic polyneuropathy.

734-P: Prevalence of Low and Borderline Levels of Vitamin B12 in Type 2 Diabetic Patients Treated with Metformin: A Cross-Sectional Study in Argentina

Background: Vitamin B12 deficiency, a common cause of megaloblastic anemia, has been associated with cognitive decline and increasing risk of depression. Metformin therapy has been associated with vitamin B12 (B12) deficiency in several populations. However, information regarding this adverse effect in Argentina populations is limited. The aim of this study was to examine the relation between metformin use and B12 status in individuals with type 2 diabetes mellitus (T2DM) in Argentina. Design and Setting: Cross-sectional study at a public university hospital. Results: At present 190 patients were included (See Table 1). Serum vitamin B12 levels were low (&amp;lt; 200 ngl/mL) in 28 patients (14.7%) and borderline (200-300 ng/ml in 48 patients (25.26 %). Only one patient showed laboratory findings consistent with anemia megaloblastic. Conclusions and Future Directions: Our study showed low or borderline levels of vitamin B12 in 14.7.3% and 25.26 % of patients, respectively. This large number of patients with low o borderline levels of B12 suggests that a high proportion of patients may be at risk of B12 deficiency related conditions. Close monitoring of B12 level, and measurement of other biomarkers of cellular B12 deficiency may help to identify these patients at risk. Disclosure C. Cela: None. M. Langus: None.

Isolated proteinuria due to CUBN homozygous mutation \u2013 challenging the investigative paradigm

BackgroundProteinuria is a common clinical presentation, the diagnostic workup for which involves many non-invasive and invasive investigations. We report on two siblings that highlight the clinically relevant functional role of cubulin for albumin resorption in the proximal tubule and supports the use of genomic sequencing early in the diagnostic work up of patients who present with proteinuria.Case presentationAn 8-year-old boy was referred with an incidental finding of proteinuria. All preliminary investigations were unremarkable. Further assessment revealed consanguineous family history and a brother with isolated proteinuria. Renal biopsy demonstrated normal light microscopy and global glomerular basement membrane thinning on electron microscopy. Chromosomal microarray revealed long continuous stretches of homozygosity (LCSH) representing ~ 4.5% of the genome. Shared regions of LCSH between the brothers were identified and their further research genomic analysis implicated a homozygous stop-gain variant in CUBN (10p12.31).ConclusionsCUBN mutations have been implicated as a hereditary cause of megaloblastic anaemia and variable proteinuria. This is the second reported family with isolated proteinuria due to biallelic CUBN variants in the absence of megaloblastic anaemia, demonstrating the ability of genomic testing to identify genetic causes of nephropathy within expanding associated phenotypic spectra. Genomic sequencing, undertaken earlier in the diagnostic trajectory, may reduce the need for invasive investigations and the time to definitive diagnosis for patients and families.

Anemia Megaloblástica, generalidades y su relación con el déficit neurológico

Las anemias megaloblásticas agrupan una serie de desórdenes que se caracterizan por el cambio morfológico de los eritrocitos y su alteración en el desarrollo y maduración a nivel de la médula ósea. Las causas de anemia megaloblástica son numerosas, pero en la mayoría de los casos es debido a deficiencia de folatos y vitamina B12. Esta última, se ve involucrada en múltiples procesos fisiológicos y metabólicos incluyendo el desarrollo del sistema nervioso central, la síntesis de neurotransmisores y la integridad celular. El déficit o ausencia de dichos compuestos genera anemia megaloblástica, una condición que deforma las células sanguíneas y causa diversos síntomas tales como fatiga, debilidad, adelgazamiento y en la primera infancia puede generar deficiencias intelectuales y trastornos motores persistentes. Se realizó una búsqueda bibliográfica con el objetivo hacer una revisión de la deficiencia de la vitamina B12 y folatos en relación con sus complicaciones a nivel neurológico.

Les vitamines du groupe B : structures et rôles dans le métabolisme, déficits nutritionnels

B vitamins are cofactors of enzymes controlling the metabolism of energetic nutriments. Under the term of B vitamin, you can find 8 vitamins from B1 to B12, i.e. B1, B2, B3, B5, B6, B8, B9 and B12. Selective avitaminosis concern mainly vitamins B1, B2, B3, B9 and B12. Total deficiency in vitamin B1 gives beriberi with heart failure and generalized polyneuritis; the defect in vitamin B2 is rare, associating troubles of skin and mucous membranes. The deficiency in vitamin B3 gives pellagra. The defects in B9 and B12 vitamins, sometimes both, are the cause of megaloblastic anemia. Chronic alcoholism as well as diseases of digestive tract with malabsorption are frequently the cause of defects in B vitamins. You can find B vitamins in cereals, fruits and vegetables, meat and fish, dairy products and eggs. Most of B vitamins can be used as drugs for the treatment of some diseases not predictable by their role in metabolism. We also use polyvitamins after surgery of the digestive tract and for patients confined to bed for a long time.

A study on prevalence and causative factors of megaloblastic anaemia in Hadoti region.

Background: Anaemia is the most common problems encountered by clinicians in Hadoti Region. The affected population includes male, female as well as children. Over the last two decades, it has been found that incidence of megaloblastic anaemia is increasing. Folic Acid and Vitamin B12 deficiency are the most common cause of megaloblastic anemia. Of these two micronutrients, Vitamin B12 deficiency is more common now, due to vegetarian life style of people. At present, Anemia control or prophylaxis program give only Iron and Folic acid. This study has been chosen to focus on this issue. The cases for increasing incidences of Folate / Vit. B12 deficiency needs to be elucidated. Objectives – To focus on the incidence of megaloblastic anaemia in Hadoti Region. & Probable Causative factors will be analysed Methods: All patients presenting to our hospital over a period of 2 months with a haemoglobin <10 g/dl and peripheral smear findings consistent with megaloblastic anaemia will be included in the study. Diet, drug intake, previous blood transfusion, presenting symptoms and other relevant history will be taken into consideration. Complete blood counts, peripheral film examination, reticulocyte count and cobalamin and folate assays will be recorded. Patients with chronic disease like renal disease, cancer, tuberculosis, liver disease etc will be excluded from the study. All data will be collected and evaluated statistically. Result: In the present study, total 500 patients who were admitted in medicine, paediatric and gynaecology ward were evaluated. All these patients met the inclusion criteria. Depending on the MCV value, serum assay and peripheral smear finding, they were categorised into 3 groups- Macrocytic, normocytic and microcytic anaemia. The normal MCV value but with megaloblastic blood film or low serum markers were considered into macrocytic anaemia. Total 100 patients were diagnosed as macrocytic anaemia. The sex distribution were-70(male), 30(female). Fifty five per cent of patients with cobalamin deficiency and 08% of patients with folate deficiency were found. All the patients were vegetarian and from middle class and low socio economic group. Conclusion: Cobalamin deficiency was responsible for megaloblastic anaemia in the majority of our patients. The supplementation program for Anemia control and prophylaxis should vary according to the regional requirements. Vitamin B12 should be included in the nutritional programme along with iron and folic acid. Awareness camp and Education program about megaloblastic anemia can be implemented for the prevention. DOI: 10.21276/AABS.2017.1313

Hematogones detected by flow cytometry in a child with vitamin B12 deficiency: A case report

Vitamin B12 deficiency is a known cause of megaloblastic anemia and bone marrow failure. Bone marrow biopsies are not frequently performed as part of the diagnostic workup and can demonstrate morphologic features that overlap with myelodysplastic syndrome (MDS) and acute leukemia. We describe a case of a dysplastic bone marrow with increased bone marrow hematogones detected by flow cytometry in a child with vitamin B12 deficiency. Hematogones are normal B cell precursors, and hyperplasia has been described in a variety of often reactive conditions and also disease. Hematogones are not typically seen in MDS. The presence of hematogones may help differentiate the dysplastic changes seen in vitamin B12 deficiency from MDS.

Vitamin B12 deficiency presenting as pancytopenia and retinopathy in a young

Deficiency of vitamin B12 (cobalamin) is a well-known cause of megaloblastic anaemia. It is a reversible cause of bone marrow failure and demyelinating nervous system disorder, hence early detection and prompt treatment of vitamin B12 deficiency is essential. After diagnosing vitamin B12 deficiency, tracking down its root cause is important in individualising the treatment approach. Helicobacter pylorirelated (H. pylori) B12 deficiency presenting as pancytopenia in pediatric age groups has been reported. However, vitamin B12 deficiency presenting as retinopathy in paediatric age groups has been rarely reported in the medical literature. We herein present the case of an adolescent male with pancytopenia and retinopathy, secondary to vitamin B12 deficiency-associated H. pylori infection.

Vitamin B12 Deficiency Mimicking Acute Leukemia in a Child

Tanyildiz HG, Malbora B, Yesil S, Candir MO, Bozkurt C, Sahin G. Vitamin B12 Deficiency Mimicking Acute Leukemia in a Child. Deficiency of vitamin B12 is an important cause of megaloblastic anemia and bone marrow depression. Morphological and functional changes in bone marrow are observed related with vitamin B12 deficiency. Most importantly dysplastic changes can be mistaken as myelodysplastic syndrome or acute leukemia. In adult cases of vitamin B12 deficiencies mimicking acute leukemia were reported. Our case is an alerting example of vitamin B12 deficiency in children mimicking acute leukemia with dysplastic findings.

Hepatosplenomegaly and pernicious anaemia.

Sir, Pernicious anaemia (PA) is the end stage of atrophic gastritis which results in the loss of parietal cells in the fundus and body of the stomach. Loss of parietal cells is associated with the failure of intrinsic factor production and results in vitamin B12 deficiency and megaloblastic anaemia. Only two cases of splenomegaly coexisting with PA have been reported, but both splenomegaly and hepatomegaly has not been reported yet [1,2]. In this report, we aimed to describe a patient with hepatosplenomegaly due to PA. To the best of our knowledge this is the first documented case of hepatosplenomegaly due to PA and totally resolved by vitamin B12 therapy. A 20-year-old male patient was admitted to our hospital with the complaints of fatigue, weakness, anorexia and palpitation. His complaints had been continued for the past one month. He had no history of another disease or medication. Pallor, subikterus, 3/6 systolic murmur in all valves, palpable splenomegaly at 4 cm below the left costal margin and palpable hepatomegaly 2 cm below the right costal margin were detected on the physical examination. Laboratory examinations revealed the following: LDH: 8440 U/L, AST: 91 U/L, ALT: 45 U/L, total bilirubin: 2.8 mg/dL, indirect bilirubin mg/dL: 2.14, Hgb: 3.9 g/dL, Hct: 12.3%, Wbc: 1400 /uL, Plt: 22000 /uL, MCV: 96 fL, corrected retikulocyte count: 0.25%, direct coombs (-), indirect coombs (-).Hepatitis markers were normal. Hepatosplenomegaly was confirmed using abdominal ultrasonography; the longitudinal spleen size was 182 mm and the craniocaudal liver size was 160 mm, and were found to be increased. The peripheral blood smear contained oval macrocytes, hypersegmented neutrophils, trombocytopenia, leucopenia and low reticulocyte count. Leukemia blasts or atypical cells were not seen on marrow aspiration and biopsy, thus hemolytic anaemia and leukemia were excluded from the differential diagnosis. Bone marrow biopsy was compatible with megaloblastic anaemia. To find the cause of megaloblastic anaemia, the level of vitamin B12 was found 30 pg/mL (197-886 pg/mL), and folic acid level was found in normal ranges. Atrophic gastritis was revealed by gastroscopy and verified in pathological examination. Anti parietal cell antibody was detected positive in blood test. There was no other endocrinopathy accompanying to B12 deficiency; TSH, cortisol, antiadrenal antibody and antithyroid peroxidase levels were found to be normal. Patient was diagnosed as pernicious anaemia due to atrophic gastritis and was given parenteral vitamin B12 treatment. Reticulocyte crisis was seen on the 5th day and leukocyte, hemoglobin, platelet levels were increased on the 3rd week of the treatment without transfusion. In the second month of the treatment there was no hepatosplenomegaly at ultrasonographic scan. The patient has no complaints during the one year follow-up while being monitored from the outpatient clinic. Even though severely anaemic patient with PA may have spleno- megaly, hepatosplenomegaly co-existing with pernicious anaemia is not considered to be a characteristic feature of PA, [1,2]. PA should be kept in mind in the differential diagnosis of hepatosplenomegaly like in our patient. According to the literature the relationship between PA and splenomegaly has been well established, but hepatomegaly of this association has not been mentioned. In our opinion, it might be resulted from extramedullary hematopoiesis, because hepatomegaly was regressed after the treatment of severe anaemia by vitamin B12. Plasma B12 levels, gastroscopy, peripheral blood smear, bone marrow biopsy should be considered, especially in pancytopenic patients with hepatosplenomegaly.

Interaction between methionine synthase isoforms and MMACHC: characterization in cblG-variant, cblG and cblC inherited causes of megaloblastic anaemia

The cblG and cblC disorders of cobalamin (Cbl) metabolism are two inherited causes of megaloblastic anaemia. In cblG, mutations in methionine synthase (MTR) decrease conversion of hydroxocobalamin (HOCbl) to methylcobalamin, while in cblC, mutations in MMACHC disrupt formation of cob(II)alamin (detected as HOCbl). Cases with undetectable methionine synthase (MS) activity are extremely rare and classified as 'cblG-variant'. In four 'cblG-variant' cases, we observed a decreased conversion of cyanocobalamin to HOCbl that is also seen in cblC cases. To explore this observation, we studied the gene defects, splicing products and expression of MS, as well as MS/MMACHC protein interactions in cblG-variant, cblG, cblC and control fibroblasts. We observed a full-size MS encoded by MTR-001 and a 124 kDa truncated MS encoded by MTR-201 in cblG, cblC, control fibroblasts and HEK cells, but only the MTR-201 transcript and inactive truncated MS in cblG-variant cells. Co-immunoprecipitation and proximity ligation assay showed interaction between truncated MS and MMACHC in cblG-variant cells. This interaction decreased 2.2, 1.5 and 5.0-fold in the proximity ligation assay of cblC cells with p.R161Q and p.R206W mutations, and HEK cells with knock down expression of MS by siRNA, respectively, when compared with control cells. In 3D modelling and docking analysis, both truncated and full-size MS provide a loop anchored to MMACHC, which makes contacts with R-161 and R-206 residues. Our data suggest that the interaction of MS with MMACHC may play a role in the regulation of the cellular processing of Cbls that is required for Cbl cofactor synthesis.